Anifrolumab (Monograph)

Brand name: Saphnelo
Drug class: Immunosuppressive Agents

Medically reviewed by Drugs.com on Jul 20, 2023. Written by ASHP.

Introduction

Anifrolumab-fnia, a type I interferon (IFN) receptor antagonist, is an immunosuppressive agent.

Uses for Anifrolumab

Anifrolumab-fnia has the following uses:

Anifrolumab-fnia is indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy.

Anifrolumab-fnia has the following limitations of use:

The efficacy of anifrolumab-fnia has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Use of anifrolumab-fnia is not recommended in these situations.

Anifrolumab Dosage and Administration

General

Anifrolumab-fnia is available in the following dosage form(s) and strength(s):

Injection: 300 mg/2 mL (150 mg/mL) in a single-dose vial.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Anifrolumab-fnia injection must be diluted prior to administration.

The recommended dosage is 300 mg as an IV infusion over a 30-minute period every 4 weeks.

If a planned infusion is missed, administer anifrolumab-fnia as soon as possible. Maintain a minimum interval of 14 days between infusions.

For complete dilution and IV administration instructions, see the full prescribing information.

Cautions for Anifrolumab

Contraindications

Anifrolumab-fnia is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia. (See Hypersensitivity Reactions, including Anaphylaxis under Cautions.)

Warnings/Precautions

Serious Infections

Serious and sometimes fatal infections have occurred in patients receiving immunosuppressive agents, including anifrolumab-fnia. Overall, the incidence of serious infections in controlled trials was similar in patients receiving anifrolumab-fnia compared with placebo, whereas fatal infections occurred more frequently in patients receiving anifrolumab-fnia.

In controlled trials, anifrolumab-fnia increased the risk of respiratory infections and herpes zoster (disseminated herpes zoster events have been reported).

Consider the benefit and risk of administering anifrolumab-fnia in patients with a chronic infection, a history of recurrent infections, or known risk factors for infection. Avoid initiating treatment with anifrolumab-fnia in patients with any clinically significant active infection until the infection resolves or is adequately treated. Instruct patients to seek medical advice if signs or symptoms of clinically significant infection occur. If a patient develops an infection, or is not responding to standard anti-infective therapy, monitor the patient closely and consider interrupting anifrolumab-fnia therapy until the infection resolves.

Hypersensitivity Reactions, including Anaphylaxis

Serious hypersensitivity reactions (including anaphylaxis) have been reported following anifrolumab-fnia administration. Events of angioedema have also been reported.

Other hypersensitivity reactions and infusion-related reactions have occurred following administration of anifrolumab-fnia. Consider premedication before infusion of anifrolumab-fnia for patients with a history of these reactions.

Anifrolumab-fnia should be administered by healthcare providers prepared to manage hypersensitivity reactions, including anaphylaxis, and infusion-related reactions. If a serious infusion-related or hypersensitivity reaction (e.g., anaphylaxis) occurs, immediately interrupt the administration of anifrolumab-fnia and initiate appropriate therapy.

Malignancy

There is an increased risk of malignancies with the use of immunosuppressants. The impact of anifrolumab-fnia treatment on the potential development of malignancies is not known.

Consider the individual benefit-risk in patients with known risk factors for the development or reoccurrence of malignancy prior to prescribing anifrolumab-fnia. In patients who develop malignancies, consider the benefit-risk of continued treatment with anifrolumab-fnia.

Immunization

Update immunizations, according to current immunization guidelines, prior to initiating anifrolumab-fnia therapy. Avoid concurrent use of live or live-attenuated vaccines in patients treated with anifrolumab-fnia.

Not Recommended for Concomitant Use with other Biologic Therapies

Anifrolumab-fnia has not been studied in combination with other biologic therapies, including B-cell-targeted therapies. Therefore, use of anifrolumab-fnia is not recommended for use in combination with biologic therapies.

Specific Populations

Pregnancy

Pregnancy Exposure Registry: A pregnancy exposure registry monitors pregnancy outcomes in women exposed to anifrolumab-fnia during pregnancy. For more information about the registry or to report a pregnancy while on anifrolumab-fnia, contact AstraZeneca at 1-877-693-9268.

Risk Summary; The limited human data with anifrolumab-fnia use in pregnant women are insufficient to inform on drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcome. Monoclonal IgG antibodies are known to be actively transported across the placenta as pregnancy progresses; therefore, anifrolumab-fnia exposure to the fetus may be greater during the third trimester of pregnancy.

In an enhanced pre- and post-natal development study with pregnant cynomolgus monkeys that received IV administration of anifrolumab-fnia, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 28 times the exposure at the maximum recommended human dose (MRHD) on an area under curve (AUC) basis.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Disease-Associated Maternal and/or Embryofetal Risk: Pregnant women with SLE are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, miscarriage, and intrauterine growth restriction. Maternal lupus nephritis increases the risk of hypertension and preeclampsia/eclampsia. Passage of maternal autoantibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block.

Animal Data: In an enhanced pre- and post-natal development study, pregnant cynomolgus monkeys received anifrolumab-fnia at IV doses of 30 or 60 mg/kg once every 2 weeks from confirmation of pregnancy at Gestation Day 20, throughout the gestation period, and continuing until 1-month post-partum (approximately Lactation Day 28). There was no evidence of anifrolumab-fnia-related maternal toxicity, embryofetal toxicity, or post-natal developmental effects. No anifrolumab-fnia-related effect on T-cell-dependent antibody response in the infants was noted up to Day 180 after birth. The no observed adverse effect level (NOAEL) for maternal and developmental toxicity was identified as 60 mg/kg (approximately 28 times the MRHD on an AUC basis). In the infants, mean serum concentrations of anifrolumab-fnia on Day 30 after birth increased with dose and were approximately 4.2% to 9.7% of the respective maternal concentrations. The anifrolumab-fnia concentrations in the infant serum were up to approximately 22 times the concentrations in the maternal milk, suggesting that anifrolumab-fnia had transferred via the placenta.

Lactation

Risk Summary: No data are available regarding the presence of anifrolumab-fnia in human milk, the effects on the breastfed child, or the effects on milk production. Anifrolumab-fnia was detected in the milk of female cynomolgus monkeys administered anifrolumab-fnia. Due to species-species differences in lactation physiology, animal data may not reliably predict drug levels in humans. Maternal IgG is known to be present in human milk. If anifrolumab-fnia is transferred into human milk, the effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to anifrolumab-fnia are unknown.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for anifrolumab-fnia and any potential adverse effects on the breast-fed child from anifrolumab-fnia or from the underlying maternal condition.

Pediatric Use

The safety and efficacy of anifrolumab-fnia in pediatric patients less than 18 years of age have not been established.

Geriatric Use

Of the 664 patients with SLE exposed to anifrolumab-fnia in clinical trials, 3% (n=20) were 65 years of age or older. The number of patients 65 years of age or older was not sufficient to determine whether they respond differently from younger adult patients.

Common Adverse Effects

Most common adverse drug reactions (incidence ≥5%) are nasopharyngitis, upper respiratory tract infections, bronchitis, infusion-related reactions, herpes zoster, and cough.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

No formal drug interaction studies have been conducted.

Based on population pharmacokinetic analysis, concomitant use of oral corticosteroids, antimalarials, immunosuppressants (e.g., azathioprine, methotrexate, mycophenolate mofetil, mycophenolic acid, mizoribine), NSAIDs, ACE inhibitors, and HMG-CoA reductase inhibitors did not significantly affect the pharmacokinetics of anifrolumab-fnia.

Actions

Mechanism of Action

Anifrolumab-fnia is a human IgG1κ monoclonal antibody that binds to subunit 1 of the type I interferon receptor (IFNAR) with high specificity and affinity. This binding inhibits type I IFN signaling, thereby blocking the biologic activity of type I IFNs. Anifrolumab-fnia also induces the internalization of IFNAR1, thereby reducing the levels of cell surface IFNAR1 available for receptor assembly. Blockade of receptor-mediated type I IFN signaling inhibits IFN responsive gene expression as well as downstream inflammatory and immunological processes. Inhibition of type I IFN blocks plasma cell differentiation and normalizes peripheral T-cell subsets.

Type I IFNs play a role in the pathogenesis of SLE. Approximately 60-80% of adult patients with active SLE express elevated levels of type I IFN inducible genes.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (patient information).
Inform patients that anifrolumab-fnia may decrease their ability to fight infections, and that serious infections, including fatal ones, occurred in patients receiving anifrolumab-fnia in clinical trials. Also inform patients that they are at increased risk of respiratory infections and herpes zoster during treatment with anifrolumab-fnia. Advise patients to contact their healthcare provider if they develop any symptoms of an infection, including fever or flu-like symptoms; muscle aches; cough; shortness of breath; burning when they urinate or urinating more often than usual; diarrhea or stomach pain; or shingles (a red skin rash that can cause pain and burning).
Inform patients that serious hypersensitivity reactions, including anaphylaxis, have been reported in patients who received anifrolumab-fnia. Instruct patients to immediately tell their healthcare provider or go to the emergency department of their nearest hospital if they experience symptoms of an allergic reaction (e.g., anaphylaxis) during or after the administration of anifrolumab-fnia. Symptoms may include swelling of the face, tongue, or mouth, breathing difficulties, and/or fainting, dizziness, or feeling lightheaded (due to a drop in blood pressure).
Inform patients that they should not receive live or live-attenuated vaccines while receiving anifrolumab-fnia. Advise patients to discuss with their healthcare provider before seeking immunizations on their own.
Advise female patients to inform their healthcare provider if they intend to become pregnant during therapy, suspect they are pregnant, or become pregnant while receiving anifrolumab-fnia. Inform women that they can find information about a pregnancy exposure registry which monitors pregnancy outcomes in women exposed to anifrolumab-fnia by calling AstraZeneca at 1-877-693-9268.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.